Progenitor cell niche senescence reflects pathology of the parotid salivary gland in primary Sjögren’s syndrome

OBJECTIVE: Salivary gland (SG) progenitor cells (SGPCs) maintain SG homeostasis. We have previously shown that in primary Sjögren’s syndrome (pSS), SGPCs are likely to be senescent, and may underpin SG dysfunction. This study assessed the extent of senescence of cells in a SGPC niche in pSS patients’ SGs, and its correlation with functional and clinical parameters. METHODS: The expression of p16 and p21 as markers of senescence in both total SG epithelium and a SGPC niche (basal striated duct cells, BSD) was examined in SGs of pSS (n = 35), incomplete pSS (n = 13) (patients with some signs of pSS, but not fulfilling all classification criteria) and non-SS sicca control (n = 21) patients. This was correlated with functional and clinical parameters. RESULTS: pSS patient SGs contained significantly more p16(+) cells both in the epithelium in general (P <0.01) and in the BSD layer (P <0.001), than non-SS SGs. Significant correlations were found in pSS patients between p16(+) BSD cells and secretion of unstimulated whole saliva, stimulated whole saliva, stimulated parotid saliva, CD45(+) infiltrate, ultrasound total score and ACR-EULAR classification score, but not with EULAR Sjögren’s syndrome disease activity index (ESSDAI) and EULAR Sjögren’s Syndrome Patient Reported Index (ESSPRI) scores. Correlations with total epithelium p16(+) cells were weaker. Incomplete pSS patients also had increased numbers of p16(+) epithelial and BSD cells. Based on protein and mRNA expression, p21(+) appears not to play a significant role in the SG in pSS. CONCLUSION: These findings suggest SGPC senescence may be an early feature of primary Sjögren’s syndrome and may contribute to defective SG function in pSS but not to systemic disease activity.